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ObjectiveTo investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health.DesignA double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients.ResultsOver 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut.ConclusionThe present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota.Trial registration number NCT02099032 and NCT02146339; Results.

Early parenteral nutrition to supplement insufficient enteral feeding during intensive care (early PN) delays recovery as compared with withholding parenteral nutrition for 1 week (late PN). To assess whether deleterious effects of early PN relate to severity of illness or to the dose or type of macronutrients. Secondary analyses of a randomized controlled trial (EPaNIC; n = 4,640) performed in seven intensive care units from three departments in two Belgian hospitals. In part 1, all patients were included to assess the effect of the randomized allocation to early PN or late PN in subgroups of patients with increasing-on-admission severity of illness. In part 2, observationally, the association of the amount and type of macronutrients with recovery was documented in those patient cohorts still present in intensive care on Days 3, 5, 7, 10, and 14. The primary end point was time to live discharge from the intensive care unit. For part 1, a secondary end point, acquisition of new infections, was also analyzed. All statistical analyses were performed by univariable and adjusted multivariable methods. In none of the subgroups defined by type or severity of illness was a beneficial effect of early PN observed. The lowest dose of macronutrients was associated with the fastest recovery and any higher dose, administered parenterally or enterally, was associated with progressively more delayed recovery. The amount of proteins/amino acids rather than of glucose appeared to explain delayed recovery with early feeding. Early combined parenteral/enteral nutrition delayed recovery irrespective of severity of critical illness. No dose or type of macronutrient was found to be associated with improved outcome. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

Background Cancer vaccines require adjuvants to induce effective immune responses; however, there is no consensus on optimal adjuvants. We hypothesized that toll-like receptor (TLR)3 agonist polyICLC or TLR4 agonist lipopolysaccharide (LPS), combined with CD4 T cell activation, would support strong and durable CD8 + T cell responses, whereas addition of an incomplete Freund’s adjuvant (IFA) would reduce magnitude and persistence of immune responses. Patients and methods Participants with resected stage IIB-IV melanoma received a vaccine comprised of 12 melanoma peptides restricted by Class I MHC (12MP), plus a tetanus helper peptide (Tet). Participants were randomly assigned 2:1 to cohort 1 (LPS dose-escalation) or cohort 2 (polyICLC). Each cohort included 3 subgroups (a-c), receiving 12MP + Tet + TLR agonist without IFA (0), or with IFA in vaccine one (V1), or all six vaccines (V6). Toxicities were recorded (CTCAE v4). T cell responses were measured with IFNγ ELIspot assay ex vivo or after one in vitro stimulation (IVS). Results Fifty-three eligible patients were enrolled, of which fifty-one were treated. Treatment-related dose-limiting toxicities (DLTs) were observed in 0/33 patients in cohort 1 and in 2/18 patients in cohort 2 (11%). CD8 T cell responses to 12MP were detected ex vivo in cohort 1 (42%) and in cohort 2 (56%) and in 18, 50, and 72% for subgroups V0, V1, and V6, respectively. T cell responses to melanoma peptides were more durable and of highest magnitude for IFA V6. Conclusions LPS and polyICLC are safe and effective vaccine adjuvants when combined with IFA. Contrary to the central hypothesis, IFA enhanced T cell responses to peptide vaccines when added to TLR agonists. Future studies will aim to understand mechanisms underlying the favorable effects with IFA. Trial registration The clinical trial Mel58 was performed with IRB (#15781) and FDA approval and is registered with Clinicaltrials.gov on April 25, 2012 (NCT01585350). Patients provided written informed consent to participate. Enrollment started on June 24, 2012.

Respiratory syncytial virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available. This was a randomized, observer-blinded, first-in-humans study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A, formulated with either the lipid and oil-based vaccine platform DepoVax (DPX-RSV[A]) or alum (RSV[A]-Alum), in healthy, 50-64-year-old individuals. Two dose levels (10 or 25 µg) of SHe with each formulation were compared to placebo. A booster dose was administered on day 56. There was no indication that the vaccine was unsafe. Mild pain, drowsiness, and muscles aches were the most common solicited adverse events (AEs), and the frequencies of the AEs did not increase after dose 2. Robust anti-SHe-specific immune responses were demonstrated in the DPX-RSV(A) 10-μg and 25-μg groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-μg group at day 421. Responses to the RSV(A)-Alum vaccines were very low. A novel antigen from the SH protein of RSV, formulated in a lipid and oil-based vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile.

Small-quantity lipid-based nutrient supplements (SQ-LNS) are promising home fortification products, but the optimal zinc level needed to improve growth and reduce morbidity is uncertain. We aimed to assess the impact of providing SQ-LNS with varied amounts of zinc, along with illness treatment, on zinc-related outcomes compared with standard care. In a placebo-controlled, cluster-randomized trial, 34 communities were stratified to intervention (IC) or non-intervention cohorts (NIC). 2435 eligible IC children were randomly assigned to one of four groups:1) SQ-LNS without zinc, placebo tablet; 2) SQ-LNS containing 5mg zinc, placebo tablet; 3) SQ-LNS containing 10mg zinc, placebo tablet; or 4) SQ-LNS without zinc and 5mg zinc tablet from 9–18 months of age. During weekly morbidity surveillance, oral rehydration salts were provided for reported diarrhea and antimalarial therapy for confirmed malaria. Children in NIC (n = 785) did not receive SQ-LNS, tablets, illness surveillance or treatment. At 9 and 18 months, length, weight and hemoglobin were measured in all children. Reported adherence was 97 ± 6% for SQ-LNS and tablets. Mean baseline hemoglobin was 89 ± 15g/L. At 18 months, change in hemoglobin was greater in IC than NIC (+8 vs -1g/L, p<0.0001), but 79.1% of IC were still anemic (vs. 91.1% in NIC). Final plasma zinc concentration did not differ by group. During the 9-month observation period, the incidence of diarrhea was 1.10 ± 1.03 and of malaria 0.54 ± 0.50 episodes per 100 child-days, and did not differ by group. Length at 18 months was significantly greater in IC compared to NIC (77.7 ± 3.0 vs. 76.9 ± 3.4 cm; p<0.001) and stunting prevalence was significantly lower in IC (29.3%) than NIC (39.3%; p<0.0001), but did not differ by intervention group within IC. Wasting prevalence was also significantly lower in IC (8.7%) than in NIC (13.5%; p = 0.0003). Providing SQ-LNS daily with or without zinc, along with malaria and diarrhea treatment, significantly increased growth and reduced stunting, wasting and anemia prevalence in young children. ClinicalTrials.gov NCT00944281.

Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

It has been suggested that intake of polar lipids may beneficially modulate various metabolic variables. The purpose of this study was to evaluate the effect of oat polar lipids on postprandial and second meal glycemic regulation, blood lipids, gastrointestinal hormones, and subjective appetite-related variables in healthy humans. In a randomized design, twenty healthy subjects ingested four liquid cereal-based test beverages (42 g of available carbohydrates) containing: i. 30 g of oat oil with a low concentration (4%) of polar lipids (PLL), ii. 30 g of oat oil containing a high concentration (40%) of polar lipids (PLH), iii. 30 g of rapeseed oil (RSO), and iv. no added lipids (NL). The products were served as breakfast meals followed by a standardized lunch. Test variables were measured at fasting and during 3 h after breakfast and two additional hours following a standardized lunch. PLH reduced glucose and insulin responses after breakfast (0–120 min) compared to RSO, and after lunch (210–330 min) compared to RSO and PLL (p < 0.05). Compared to RSO, PLH resulted in increased concentrations of the gut hormones GLP-1 and PYY after the standardized lunch (p < 0.05). The results suggest that oat polar lipids have potential nutraceutical properties by modulating acute and second meal postprandial metabolic responses.

Nutrition and the home environment contribute to the development of the autonomic nervous system (ANS). However, no study has examined the long‐term effects of prenatal and postnatal small‐quantity lipid‐based nutrient supplements (SQ‐LNS) and home environment on ANS regulation. We investigated the effect of early‐life SQ‐LNS and home environment on ANS regulation at 9–11 years. Participants were children born to women who participated in a randomized controlled trial in Ghana from 2009 to 2014. Women were randomized to receive daily, from pregnancy until delivery, either SQ‐LNS, multiple micronutrients (MMN) or iron and folic acid (IFA) followed by SQ‐LNS, MMN or placebo, respectively, until 6 months postpartum. Infants in the SQ‐LNS group received SQ‐LNS from 6 to 18 months. Quality of home environment was observed at 4–6 and 9–11 years. At 9–11 years, 965 children had their respiratory sinus arrhythmia (RSA) and pre‐ejection period (PEP) measured at baseline and during two inhibitory control tasks, the RACER Simon and Emotion Go/No‐Go (EGNG) tasks. PEP reactivity to the RACER Simon task was greater in the MMN (−2.54 ± 4.45, p = 0.016) and SQ‐LNS (−2.31 ± 4.94, p = 0.093) groups than in the IFA group (−1.57 ± 3.51). A better home environment at 4–6 predicted longer baseline PEP (β = 0.13, 95% CI: 0.02, 0.23, p = 0.016) and more PEP reactivity during the EGNG task (β = −0.06, 95% CI: −0.00, −0.02, p = 0.001). Prenatal micronutrient supplementation appears to increase SNS reactivity. Children raised in disadvantaged early home environments had more tonic SNS activation and less SNS reactivity, suggesting a predisposition for stronger fight‐or‐flight activation and less likelihood to modulate arousal in response to acute situations. Trial Registration: ClinicalTrials.gov identifier: NCT00970866 A long‐term follow‐up study of a randomized controlled trial found that children of mothers who received either prenatal and postnatal small‐quantity lipid‐based nutrient supplements or multiple micronutrient supplements had better cardiac sympathetic activity compared to those who received iron and folic acid. A better early childhood environment also predicted better sympathetic activity. Summary Evidence for the effect of prenatal and postnatal nutrient supplements and the home environment on autonomic nervous system development in children is needed. Children of mothers who received either small‐quantity lipid‐based nutrient supplements or multiple micronutrient supplements had better cardiac sympathetic activity compared to those who received iron and folic acid. The early childhood environment was also significantly associated with SNS regulation at 9–11 years. These findings highlight the importance of improving both early nutrition and the quality of the childhood home environment to improve ANS outcomes for children.

Dyspeptic symptoms are common with aspirin and clinicians frequently recommend that it be taken with food to reduce these side effects. However, food can interfere with absorption, especially with enteric-coated aspirin formulations. We evaluated whether food interferes with the bioavailability of a new, pharmaceutical lipid-aspirin complex (PL-ASA) liquid-filled capsule formulation. In this randomized, open label, crossover study, 20 healthy volunteers fasted for ≥ 10 h and then randomized as either “fasted”, receiving 650 mg of PL-ASA, or as “fed”, with a standard high-fat meal and 650 mg of PL-ASA 30 min later. After a washout of 7 days, participants crossed over to the other arm. The primary outcome was comparison of PK parameters of the stable aspirin metabolite salicylic acid (SA) between fasted and fed states. Mean age of participants was 36.8 years and 55% were male. The ratios for the fed to fasted states of the primary SA PK parameters of AUC0−t and AUC0−∞ were 88.7% and 88.8% respectively, with 90% confidence intervals between 80 and 125%, which is consistent with FDA bioequivalence guidance. Mean peak SA concentration was about 22% lower and occurred about 1.5 h later in the fed state. Food had a modest effect on peak SA levels and the time required to reach them after PL-ASA administration, but did not impact the extent of exposure (AUC) compared with intake in a fasted state. These data demonstrate that PL-ASA may be co-administered with food without significant impact on aspirin bioavailability.Clinical Trial Registration:http://www.clinicaltrials.gov Unique Identifier: NCT01244100

The co‐existence of childhood stunting and obesity is a public health problem in Guatemala and Latin America. The objective of this study was to assess the effects of unsweetened small‐quantity lipid‐based nutrient supplements (SQ‐LNS) coupled with a behavior change communication (BCC) strategy on the double burden of malnutrition. We conducted a three‐arm randomized‐control trial with two‐stage cluster sampling of households with children under 4.5 months or a mother in the third trimester of pregnancy at baseline from 76 communities in Baja‐Verapaz, Guatemala. Some 1268 households were randomly assigned to SQ‐LNS or micronutrient powders (MNPs) paired with a multilevel participatory‐ludic BCC strategy, or to MNPs only. Measures of mothers' nutrition knowledge and practices were collected at baseline and endline. Children's height, weight, and hemoglobin concentration were measured at endline. Treatment effects were estimated using regression models. The BCC strategy boosted caregiver nutrition knowledge from 4.2 (95% CI: 2.7, 5.7) to 4.6 percentage points (95% CI: 3.1, 6.1). Significant effects on nutrition practices of 3.0 percentage points (95% CI: 1.2, 4.8) were found only for caregivers with children receiving SQ‐LNS. We found no detectable treatment effects on stunting or anemia. However, children exposed to SQ‐LNS and the BCC strategy were 2.6 percentage points (95% CI: −5.0, −0.2) less likely to be overweight or obese (54.1% lower than the group receiving MNPs only). An intervention coupling a multilevel participatory‐ludic BCC strategy with the use of unsweetened SQ‐LNS holds promise for the prevention of childhood overweight and obesity, yet complementary interventions are required to address non‐nutritional factors related to stunting in Guatemala. Coupling a multilevel participatory‐ludic BCC strategy with the use of unsweetened SQ‐LNS reduces the risk of being overweight or obese in infants and young children from Guatemala. Yet, complementary interventions to address non‐nutritional factors related to stunting in Guatemala are needed. Summary Co‐existence of childhood stunting and overweight and obesity is a public health problem in Guatemala and the Latin American region. Coupling a multilevel participatory‐ludic BCC strategy with the use of SQ‐LNS reduces the risk of being overweight or obese in young children. More research on the potential pathways of SQ‐LNS to prevent overweight and obesity is needed. BCC plus supplementation with SQ‐LNS or MNPs had no effect on stunting, underweight, or anemia in children from Baja Verapaz, Guatemala. Complementary behavioral, economic, or environmental interventions are required to address non‐nutritional factors related to stunting in Guatemala.